There were no guidelines for fecal grafting. Then a patient died.

In June, after one patient died and another had a fecal graft containing drug-resistant bacteria, the Food and Drug Administration stepped in and established new guidelines for the procedure.

The guidelines established that both donors and your stool should be screened for the presence of "multidrug-resistant organisms". They were included in a warning issued by the agency, which found that the two patients had weakened the immune system and that the donor chair they received had not been tested for the particular superbug that made them ill.

However, no additional information was provided on how the chair was processed, how it was administered to the patient, or how he was treated.

The announcement raised more questions than she answered. Boss among them: what exactly happened in the two cases? And given the increasing threat of drug-resistant bacteria, why did not these guidelines already exist?

To the frustration of many physicians, the FDA has still remained mother in the details of the cases. Beyond the brief safety alert, the agency did not provide any additional information, presumably because the patients were participating in a clinical trial, which meant the information was privileged.

As to the question why there were no guidelines that required a review of the long history of the procedure.

History of fecal grafting

Until a few years ago, fecal microbiota transplants (FMTs) were completely unregulated. The procedures are considered to fall under the heading "Practice of Medicine", a section that allows physicians to use treatments that have not been approved and may not even have a very long track record.

But FMTs are actually doing this I have a long track record. As early as the 1950s, doctors in the US began transplanting stools from healthy donors into patients with life-threatening diarrhea caused by infection with a nasty bacterium called C. difficile. The transplants worked and the patients got better.

The reason for the success of the procedure was that the patients fell ill first: all had a history of extensive antibiotic treatments.

"The doctors reasoned that the problem was that antibiotics had killed the normal microbes in the gut and had somehow disrupted the normal ecosystem there, allowing poor bacteria to flourish," Dr. Alexander Khoruts, gastroenterologist and professor of medicine at the University of Minnesota. "They thought that this could possibly be reversed by adding [gut bacteria] from healthy people through enemas. It worked spectacularly well. "

The success of the treatment became known, and doctors across the country began to apply the technique, although there were no clinical trials that could prove their value.

That changed in January 2013 As a study published in the New England Journal of Medicine showed that FMT was so effective in treating C. diff that researchers did not need to enroll new patients for their study because it was unethical would be to have a control group that did not receive the drug treatment.

In the meantime, specialists began to optimize how the donated chair was processed. "Essentially, all food, fiber and other substances are filtered out, and all that's left is the fluid with the bacteria," Dr. Daniel Uslan, Clinical Chief of Infectious Diseases at UCLA Health.

Nowadays FMTs can also be given orally: Doctors have refined the process so that the bacteria fit into a capsule that patients can swallow.

As of 2012, a non-profit company called Open Biome collected and processed donor chairs and sold their "product" to gastroenterologists who did not want to do it themselves.

However, the FDA has not yet established guidelines that physicians should seek donors and their stools before transplanting. Although many vendors have looked for specific pathogens, it has also been suggested that the stool in healthy donors was unlikely to contain any dangerous bacteria.

Drug Designation

Following the publication of New England In February 2013, the agency convened a workshop that concluded that the best way to label FMT as an investigational medicinal product was only in the EU may be clinical trials. (Until a drug is approved by the FDA, it can only be used in clinical trials.)

The decision resulted in a backlash from specialists who knew that many patients in need of treatment were unable to to participate in these studies. [19659002] In response, the FDA eased slightly. The Agency has decided to authorize the use of FMT outside of clinical trials for a specific group of patients, for those with C. diff infections who have not disappeared with standard antibiotic treatment. Doctors, for their part, had to be sure to explain the potential risks of the procedure.

At the time, no one, including the FDA, knew exactly what these risks might be – in fact, it's always a problem with uninvestigated and unproven treatment – but according to Khoruts, the FDA's biggest worry was that risk of infection.

Despite the margin of discretion, many professionals did not view the treatment as a drug because of the possibility that it did. In the future, companies would develop products marketed as a microbiomer set and then demand so much that some patients could not afford this. (Still, current treatment can be costly: Open Biome, for example, charges between $ 1,595 and $ 1,950 for her processed stool.)

An alternative, Khoruts says, would be the treatment of FMTs such as organ transplants. In other words, physicians would continue to treat patients, some even in their own trials, but without FDA regulation and with less likelihood that a drug maker will be seen.

However, in the view of the FDA, the name of the drug was only "We have found it most sensible to regulate it as a biological drug," Dr. Peter Marks, Director of the Center for Evaluation and Research of Biologics at the FDA. "In many ways, it's like a drug. Is it the perfect analogy? I will be the first to admit that it is not perfect. "

With drug designation, therapy was more likely to be tested in rigorous clinical trials," said Marks. In these studies, it would need to be evaluated for both efficacy and safety, and scientists could explore how to best administer the treatment.

"There are many things in the history of medicine that made the preliminary data look good. Randomized, controlled trials found that they did not help and potentially harm people," Marks told NBC News. "We want to protect public health while ensuring that people receive the treatments they need."

The popularity of FMT has undoubtedly increased dramatically in recent years. At clinicaltrials.gov, there are more than 300 registered studies of FMT for a variety of diseases, many of which go far beyond their original uses, including graft rejection, obesity and cancer, as well as some of the more likely gastrointestinal disorders disorders such as irritable bowel syndrome and ulcerative colitis.

For Dr. med. Ari Grinspan is looking for closer monitoring, especially after a death involving FMT.

We can not use it badly, "said Grinspan, Deputy Professor of Medicine in the Department of Gastroenterology at the Icahn School of Medicine on Mount Sinai. "This is a bit like a blood donation in the 80's, when we did not know that we should check for hepatitis B or HIV."